Background Di(2-ethylhexyl) phthalate (DEHP) is the most prevalent environmental endocrine disruptor among phthalate acid esters (PAEs) worldwide. Previous studies have indicated that exposure to DEHP may disrupt glucose metabolism. Objective To investigate the impact of DEHP on glucose homeostasis in rats, focusing on oxidative stress-induced impairment of autophagy in islet β cells. Methods Forty male SD rats were randomly assigned to four groups, receiving DEHP doses of 0, 187, 375, and 750 mg·kg⁻¹ for 12 weeks. Oral glucose tolerance (OGTT) and insulin tolerance tests (ITT) were conducted 24 h after the final exposure. Pancreatic microstructural alterations were assessed using hematoxylin and eosin (HE) staining and transmission electron microscopy (TEM). Commercial ELISA kits were employed to quantify the levels of insulin, adenosine triphosphate (ATP), and adenosine monophosphate (AMP) in rat serum, as well as the protein expression level of activated caspase-3 in pancreatic tissue. Additionally, commercial microplate kits were utilized to measure the concentration of reduced glutathione (GSH) in serum, the activity of superoxide dismutase (SOD) using water-soluble tetrazolium salt-1, the content of malondialdehyde (MDA) by thiobarbituric acid method, and the level of reactive oxygen species (ROS) in pancreatic tissue by chemical fluorescence method. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure sequestosome1 (SQSTM1/p62), Beclin1, microtubule-associated protein 1 light chain 3 (LC3), and cysteinyl aspartate specific proteinase-8 (Caspase-8) mRNA levels. Western blot analysis was applied to detect the protein relative expression levels of p62, Beclin-1, LC3-I, LC3 II, AMPK, p-AMPK, mTOR, p-mTOR, ULK1, and Caspase-8. Results Compared to the 0 mg·kg⁻¹ DEHP group, the 750 mg·kg⁻¹ DEHP group exhibited a significant increase in fasting blood glucose levels at 2, 4, 6, and 12 weeks (P<0.05). The OGTT showed that, following high-glucose gavage, the 187 mg·kg⁻¹ DEHP group had elevated blood glucose at 30 min (P<0.05), the 375 mg·kg⁻¹ DEHP group showed increased glucose levels at 15, 30, and 180 min (P<0.05), and the 750 mg·kg⁻¹ DEHP group exhibited elevated levels at 15, 30, 60, and 180 min (P<0.05). The 375 and 750 mg·kg⁻¹ DEHP groups demonstrated significantly increased OGTT area under the curve (AUC) values (P<0.05). In contrast, ITT results indicated no significant differences in blood glucose levels or AUC among the DEHP exposure groups at all time points (P>0.05). Compared to the 0 mg·kg⁻¹ DEHP group, the 750 mg·kg⁻¹ DEHP group exhibited significantly higher HOMA-IR levels and markedly lower HOMA-ISI values (P<0.05). HE and TEM showed that in each DEHP exposure group, the number of islet cells decreased, the islet area reduced, and chromatin condensation occurred. The endocrine granules in the cytoplasm of islet β cells decreased, and there were varying degrees of widening of the nuclear membrane gap, flattening and expansion of the Golgi complex, and expansion of the endoplasmic reticulum. Ribosome separation was observed, and autophagosomes were visible. In the 375 and 750 mg·kg⁻¹ DEHP groups, the mitochondria were deformed to varying degrees, and some cristae structures disappeared, presenting vacuolization. Moreover, the chromatin condensation in the nuclei was more severe in the 750 mg·kg⁻¹ DEHP group. The serum SOD activity was significantly elevated in the 750 mg·kg⁻¹ DEHP group (P<0.05). Both the 375 mg·kg⁻¹ and 750 mg·kg⁻¹ DEHP groups exhibited a significant increase in the relative ROS content in pancreatic tissue (P<0.05). In DEHP-treated groups, the MDA content increased (P<0.05), while the GSH content decreased (P<0.05). Additionally, in the 750 mg·kg⁻¹ DEHP group, the AMP/ATP ratio in serum was significantly raised (P<0.05), and the expression of cleaved Caspase-3 protein in pancreatic tissue was also significantly increased (P<0.05). The relative mRNA levels of p62, Beclin-1, LC3, and Caspase-8 in the pancreatic tissue of rats exposed to DEHP were significantly elevated (P<0.05). The relative expression levels of p-AMPK/AMPK, p-ULK1/ULK1, and Beclin-1 proteins in the DEHP-treated groups were significantly increased (P<0.05). In the 375 mg·kg⁻¹ and 750 mg·kg⁻¹ DEHP treatment groups, the relative expression levels of p62, LC3 II/LC1, and Caspase-8 proteins were significantly increased (P<0.05), while the relative expression level of p-mTOR/mTOR was significantly decreased (P<0.05). Conclusion DEHP can disrupt glucose homeostasis by inducing oxidative stress, which subsequently activates autophagy via the ROS/AMPK/ULK1 pathway, impairing autophagic flux and promoting apoptosis of islet β cells, ultimately decreasing their function and number.

Objective To investigate doctors'knowledge and differences in islet function assessment methods in China.Methods This is a cross-sectional study that conducted by online questionnaire survey.Demographic data,examination items,blood collection point of OGTT,detection method,kit type and follow-up frequency were collected and compared among doctors in different regions,different levels of hospitals,different specialties and different titles.Results 79.2%and 85.1%of physicians believed that the levels of insulin and C-peptide should be measured at the same time to assess islet function in patients with newly diagnosed and follow-up diabetes mellitus patients.Endocrinologists preferred to access insulin and C-peptide at the same time(P<0.05).56.0%of physicians chose bread meal test for T1DM patients and 54.7%for T2DM patients.Compared with non-specialists,endocrinologists preferred to commit bread meal test to T1DM patients(61.4%vs 41.0%,P<0.05).In addition,for the islet function assessment of new-onset diabetes patients,7.6%of physicians chose the six-point method(0,30,60,90,120,180 min),27.3%selected the five-point method I(0,30,60,120,180 min),8.5%selected the five-point method II(0,30,60,90,120 min),9.8%selected the four-point method I(0,30,60,120 min),10.3%selected the four-point method II(0,60,120,180 min),13.8%chose the three-point method(0,60,120 min)and 13.4%chose the two-point method(0,120 min).At the time of follow-up assessment,the above selection rates were 5.3%,20.4%,6.4%,6.6%,9.4%,15.8%and 24.1%,respectively.In terms of the frequency of assessment,39.2%of doctors assessed islet function once a year and 24.7%once every six months.Specialists preferred to assess islet function once a year,and physicians with senior titles chose to assess islet function more variably.Conclusion At present,there are still great differences in assessment methods of islet function in China.It is of great significance for the clinical diagnosis and treatment of diabetes to understand the differences in the selection of islet function assessment methods among doctors in different regions,specialties and job titles.

Objective:To compare with video-fluoroscopic swallowing function test(VFSS),so as to evaluate the application value of ultrasonography in the test of dysphagia after stroke.Methods:A total of seventy-two patients with dysphagia after stroke who admitted to The Second Affiliated Hospital of Hainan Medical University from January 2022 to July 2023 were selected as cases group,and a total of 45 healthy aged with normal swallowing function were selected as healthy control group at the same time.All of them underwent video X-ray fluoroscopic examination of swallowing function and quantitative assessment of ultrasound.Quantitative assessment of ultrasound was performed by twice to compare the internal consistency of ultrasound test.Meanwhile,the correlation between ultrasound and VFSS results was tested to verify the validity of ultrasound quantitative assessment.The VFSS was used as gold standard to analyze the sensitivity and specificity of ultrasound assessment.The differences of abnormal grade of Geniohyoid muscle;movement time,movement distance and the change of tongue muscle thickness of semi quantitative description of ultrasound between two groups were compared.Results:The intra group correlation coefficient(ICC),movement time,movement distance and movement speed of grade description of muscle abnormalities of cases group were respectively 0.90,(1.743±0.235)s,(6.323±0.823)mm and(3.826±0.778)mm/s,which intra reliabilities were high correlation(ICC=0.90,0.82,0.87,0.85,P＜0.01),which inter reliabilities of these indicators were high correlation(ICC=0.86,0.85,0.88,0.87,P＜0.01),respectively.The positive results of ultrasound test highly correlated with the results of VFSS examination(r=0.91,P＜0.01).The movement distance,the average movement speed and the changes of the thickness of tongue muscle in patients of cases group were significantly smaller than those of healthy control group,but the movement time was larger than that of healthy control group(t=9.03,30.49,-7.02,22.69,P＜0.05),respectively.The results of the ultrasound on the muscles of all patients in cases group existed abnormality.Conclusion:Ultrasound technique can quantitatively assess dysphagia after stroke.Compared with VFSS technique,ultrasonography can measure and determine the related data of the movement of swallowing muscle,and dynamically record movement parameters of geniohyoid muscle and the changes of the thickness of tongue muscle.At the same time,it can detect the grade of muscle abnormalities of patients with dysphagia,which will contribute to further explore the potential pathological mechanism about muscle,and promote the healthy management for patients with dysphagia.

Objective To investigate the effects of microgravity environment on hibernating myoblasts.Methods Hibernating myoblasts were cultured under real and simulated microgravity conditions for 10 days.RNA-seq analysis and immunofluorescence are used to analysis the impact of microgravity environment on cell growth and gene expression of myoblasts.Results Under the microgravity conditions,genes associated with proliferation were upregulated.Under simulated microgravity,there were more and higher proportion of Ki67 positive cells compared to normal gravity conditions.Conclusion The microgravity environment promotes the proliferation of hibernating myoblasts.

Objective:To explore the impact of coronary CT angiography (CCTA) image quality and related factors on the diagnostic performance of CT-derived fractional flow reserve (CT-FFR).Methods:Based on the CT-FFR CHINA trial, the prospective multicenter trial enrolled patients with suspected coronary artery disease who underwent CCTA, CT-FFR and FFR measurement. The subjective and objective assessments of CCTA image were performed on a per-vessel level. The objective assessments included the enhancement degree of coronary artery, the signal-to-noise ratio (SNR) of the aortic root. We used χ 2 test and DeLong test to compare the diagnostic performance of CT-FFR with FFR as the reference standard in different subjective groups (non-artifact vs. artifact), enhancement degree of coronary artery groups (≤400 vs. 401-500 vs.>500 HU), SNR of the aortic root groups (≤16.9 vs.>16.9), body mass index (BMI) groups (<25 kg/m 2 vs.≥25 kg/m 2) and heart rate groups (<75 bpm vs.≥75 bpm). FFR and CT-FFR values≤0.80 was identified as myocardial ischemia. Results:The study enrolled 317 patients with 366 vessels. All target vessels in CCTA images were successfully analyzed by CT-FFR. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value and AUC of the non-artifact group were 90.45%, 86.75%, 93.10%, 90.00%, 90.76% and 0.928, respectively, and those of the artifact group were 83.23%, 87.21%, 79.01%, 81.52%, 85.33% and 0.869, respectively. The differences in accuracy and specificity were statistically significant (χ 2=4.23, P=0.040; χ 2=8.55, P=0.003). The diagnostic efficacy of CT-FFR had no statistically significant differences among different objective groups (all P>0.05). Conclusions:The artifact of CCTA image has an effect on CT-FFR in the diagnosis of myocardial ischemia. The degree of vascular enhancement, SNR, BMI, and heart rate have no significant effect on the diagnostic performance of CT-FFR.

Objective:To investigate the efficacy of treatment of Sanders Ⅱ & Ⅲ calcaneal fractures with an absorbable stick plus Kirschner wire through the tarsal sinus incision.Methods:From July 2017 to May 2020, 37 patients with 42 Sanders Ⅱ & Ⅲ calcaneal fractures were treated with an absorbable stick plus Kirschner wire through the tarsal sinus incision at The Third Ward of Department of Traumatic Orthopeadics, The Sixth Hospital of Ningbo. There were 25 males and 12 females, with an age of (48.2±5.6) years (from 20 to 69 years). The fractures were at the left side in 12 cases, at the right side in 20 and at bilateral sides in 5. By Sanders classification, 20 fractures were type Ⅱ and 22 ones type Ⅲ. Fracture union time and complications were recorded. Their B?hler and Gissane angles were compared between preoperation, postoperation and the last follow-up. The range of motion of the subtalar joint was evaluated by the Morrey method at 6 months postoperation. The functional recovery was evaluated by the American Society of Foot and Ankle Surgery (AOFAS) ankle-hindfoot score at 12 months postoperation.Results:The 37 patients were followed up for (15.2±2.7) months (from 13 to 18 months). There were no such complications as incision skin necrosis, Kirschner wire deformation, loss of fracture reduction or Kirschner wire infection. The anatomical morphology of the calcaneus was restored satisfactorily in the 37 patients. At preoperation, postoperation and the last follow-up, the B?hler angles were 13.3°±1.6°, 32.5°±5.5° and 32.7°±5.4° and the Gissane angles 78.3°±6.7°, 127.2°±6.7° and 128.0°±6.4°, respectively, showing significant differences between the preoperative and postoperative values ( P<0.05) but no significant differences between postoperation and the last follow-up ( P>0.05). The range of motion of the subtalar joint at 6 months postoperation was slightly limited in 25 cases and moderately limited in 12 cases, giving a rate of moderate and above limitation of 32.4% (12/37). By the AOFAS ankle-hindfoot score at 12 months postoperation, 12 cases were excellent, 21 ones good and 4 ones fair, giving a good to excellent rate of 89.2% (33/37). Conclusion:Treatment with an absorbable stick plus Kirschner wire through the tarsal sinus incision may lead to fine clinical efficacy for Sanders Ⅱ & Ⅲ calcaneal fractures.

Objective:To compare the efficacy and safety of robot-assisted laparoscopic and laparoscopic partial nephrectomy (RAPN and LPN) for patients with completely endophytic renal tumor.Methods:A total of 73 patients with completely endophytic renal tumor receiving RAPN (n=29) or LPN (n=44) in our center between January 2015 and June 2021 were retrospectively collected. There were 21 males and 8 females in RAPN group. The average age was 48.6±13.7 years old, average tumor size was 2.9±0.9 cm with 13 left tumors and 16 right tumors, average R. E.N.A.L. score was 9.2±1.0, and average preoperative eGFR was 82.6±10.7 ml/(min·1.73 m 2). There were 27 males and 17 females in LPN group. The average age was 50.1±12.3 years old, average tumor size was 2.9±0.9 cm with 24 left tumors and 20 right tumors, average R. E.N.A.L. score was 9.1±1.3, and average preoperative eGFR was 81.7±9.6 ml/(min·1.73 m 2). There was no significant difference in above variables between two groups. The operative time, warm ischemia time, blood loss, postoperative complication, postoperative hospital stay and postoperative 3 months renal function of two groups were compared. Results:All 73 patients successfully underwent RAPN or LPN and no patient converted to radical nephrectomy or open surgery. There was no significant difference in operation time [140(80, 160) min vs. 150 (90, 180) min, P=0.264], intraoperative estimated blood loss[150 (100, 200)vs. 180 (120, 200) ml, P=0.576]and postoperative hospital stay (7.0±2.7 vs. 7.4±2.1 days, P=0.480) between two groups. Compared with LPN group, RAPN group had obvious less warm ischemia time (23.1±3.3 vs. 27.6±4.7 min, P<0.001). No obvious complication occurred in RAPN group and one case with postoperative hemorrhage occurred in LPN group. No positive margin occurred in either group. There was no difference in renal function 3 months after operation between the two groups [73.2±6.3 vs.70.5±7.6ml/(min·1.73 m 2), P=0.117]. The median follow-up period was 22.6 months with no tumor recurrence or metastasis. Conclusions:For experienced surgeons, both RAPN and LPN are safe and feasible for patients with completely endophytic renal tumor. Compared with LPN, RAPN has advantages of perioperative curative effect, which could reduce the operating difficulty and shorten the warm ischemia time.

Objective:To investigate the efficacy of the posterior axillary approach combined with the deltoid pectoralis major approach in the treatment of proximal humeral fracture combined with lower glenoid fracture.Methods:From July 2019 to September 2021, 7 patients were treated at Department of Traumatic Othopeadics, The Sixth Hospital of Ningbo for proximal humeral fracture combined with lower glenoid fracture by internal fixation via the posterior axillary approach combined with the deltoid pectoralis major approach. They were 2 males and 5 females, aged from 51 to 78 years (average, 62.9 years). All fractures were closed ones. According to the Neer classification for the proximal humeral fractures, there were one case of type Ⅱ, one case of type Ⅲ, 3 cases of type Ⅳ and 2 cases of type Ⅵ. According to the Ideberg classification for the glenoid fractures, 5 cases were type Ⅰ and 2 cases type Ⅱ. The anteroposterior, lateral and axillary X-ray films of the affected shoulder were taken at 6 and 12 weeks, and 6 and 12 months after operation to follow up fracture healing and occurrence of complications. The Constant-Murley shoulder joint scores and the Disability of Arm Shoulder and Hand (DASH) scores for the upper limb dysfunction were recorded at the last follow-up for all patients.Results:All the 7 patients were followed up for 8 to 15 months (mean, 11.9 months). Bone union was achieved after an average of 4.3 months (from 3 to 6 months) in all patients. None of the functional activities was affected in all by postoperative shoulder joint instability, incision infection or axillary scar hyperplasia. At the last follow-up, their Constant-Murley scores averaged 83.4 points (from 55 to 92 points), and their DASH scores 13.5 points (from 4.2 to 33.3 points).Conclusion:In the treatment of proximal humeral fracture combined with lower glenoid fracture, the posterior axillary approach combined with the deltoid pectoralis major approach can lead to fine early curative efficacy due to their advantageous possibilities to allow for easy fracture reduction, reliable fixation and early rehabilitation.

OBJECTIVE：To systematically evaluate the effectiveness and safety of nicorandil combined with atorvastatin calcium in the treatment of unstable angina pectoris ，and to provide reference for clinical treatment. METHODS ：Retrieved from PubMed，Cochrane Library ，Embase database ，CBM，VIP，CNKI and Wanfang database ，randomized controlled trials （RCTs） about nicodil combined with atorvastatin calcium in the treatment of unstable angina pectoris were collected from the inception until Jan. 3rd，2021. The included studies were screened and evaluated with modified Jadad scale. Meta-analysis was performed by using Rev Man 5.3 software. RESULTS ：A total of 10 RCTs were included ，involving 1 123 patients. Meta-analysis results showed that compared with atorvastatin calcium group ，nitcodil combined with atorvastatin calcium group significantly increased angina response rate [OR ＝3.44，95％CI（2.35，5.04），P＜0.001]，the rate of electrocardiogram improvement [OR ＝4.93，95％CI（2.88， 8.43），P＜0.001]，and significantly reduced MMP- 9 level [SMD ＝－4.21，95％CI（－4.63，－3.80），P＜0.001]，incidence of recurrent angina pectoris [OR ＝0.30，95％CI（0.12，0.71），P＝0.006]，myocardial infarction rate [OR ＝0.27，95％CI（0.08，0.89）， P＝0.03]，the incidence of adverse cardiovascular events [OR ＝0.34，95％ CI（0.21，0.55），P＜0.001]. CONCLUSIONS ： Nicorandil combined with atorvastatin calcium shows better efficacy in the treatment of unstable angina pectoris in terms of effective rate of angina pectoris ，improvement rate of cardiogram ，MMP-9 level，incidence of recurrent angina pectoris and the incidence of myocardial infarction ，and has better safety in the incidence of adverse cardiovascular events. Due to the limitation of included studies ，it remains to be verified by RCT with large sample，multi-center and high quality.

Objective:To explore risk factors of death in type A intramural hematoma (IMH) patients with conservative therapy and provide important information for clinical risks stratification and decisions-making.Methods:This retrospectively study enrolled 130 patients diagnosed with type A IMH in the first CT examination at Fuwai Hospital of Chinese Academy of Medical Sciences and only received conservative therapy between September 2009 and June 2018. Baseline clinical and CT characteristics were recorded. All patients enrolled were followed up. The endpoint was aortic disease-related death, patients were divided into endpoint group and non-endpoint group according to whether or not an endpoint event occurs. Difference between two groups of normally distributed continuous variables, non-normally distributed continuous variables and categorical variables were tested by independent sample t test, Mann-Whitney U test and chi-square test or Fisher′s exact test, respectively. Independent risk factors related to outcomes were assessed with Cox regression analysis and survival analysis. Results:In baseline CT data, the mean value of the maximum aortic diameter (MAD) was (49.2±6.9) mm, and the median value of the maximum hematoma thickness (MTH) was 11.0 (8.5, 13.2) mm. There were 56 and 30 patients with ulcer-like projection (ULP) and intramural blood pool (IBP), respectively, which including 36 patients with ULP of ascending aorta, 51 patients with pericardial effusion and 50 patients with pleural effusion. During a median follow-up time of 1 050 (242, 1 949) days, 26 patients experienced aortic disease-related death. Compared with non-endpoint group patients, patients who experienced aortic disease-related death showed older age and larger MAD( t=2.363, 3.640, P=0.020,<0.001), higher proportion of aortic atherosclerosis, ULP and pericardial effusion (χ 2=5.275, 6.596, 9.325, P=0.022, 0.010, 0.002).In Cox regression multivariate analysis shows that aortic atherosclerosis [hazard ratio (HR)=3.48, P=0.043], ULP (HR=2.66, P=0.019) and pericardial effusion (HR=2.49, P=0.030) were independent risk factors for aortic disease-related death. Conclusions:Aortic atherosclerosis, ULP and pericardial effusion are independent predictors of subsequent aortic disease-related death for type A IMH patients with conservative therapy, identifying these risk factors is helpful for further risk stratification and decisions-making.